New insight into neurobiology of alcohol abuse

View:28 Time:2017-09-11

Scientists have identified a protein implicated in alcohol intake, seeking, and reward. The finding would help to find strategies for solving the problem of excessive drinking, which kills 3.3 million people annually.

Addiction is a condition that a person continues to consume a substance or do a thing even though the long term effect of the substance or thing is harmful. Many types of substances and behaviors can cause addiction, such as alcohol, cocaine, nicotine, opiate, eating, gambling, sex, and shopping. Among these factors, alcohol (or ethanol) might be the most significant, as it is legal and easy to get. There is no doubt that our society pays a significant cost for alcohol abuse. Alcohol drinking is linked to many harmful consequences, such as health complications, traffic accidents, workplace-related problems, family and domestic problems, and interpersonal violence.

However, there are a limited number of medications to help treat alcohol use disorder. Novel, more effective therapies are still in need.

Dr. Dorit Ron, Professor in the Department of Neurology at the University of California, has been studying the molecular neurobiology of alcohol abuse for a long time. Dr. Ron and colleagues previously have found that a protein, called mTORC1, appears to be involved in different types of drug abuse. Drinking too much alcohol increases the activity of mTORC1 in a brain structure crucial for the reward circuitry known as the nucleus accumbens (NAc), and the increased mTORC1 activity is linked to alcohol seeking.

Additionally, Dr. Ron's team has also discovered that using the immunosuppressant drug rapamycin to inhibit mTORC1 activity resulted in reduced alcohol drinking in experimental animals. Importantly, rapamycin did not affect the animals' taste for other substances like sugar water. Despite its effectiveness, rapamycin can not be used in humans because of its remarkable adverse effects.

In the latest study, Dr. Ron and colleagues set to find molecules associated with mTORC1 activity. With the help of the unbiased RNA-seq approach, they identified the protein Prosapip1 as a new downstream target of mTORC1. They demonstrated that Prosapip1 expression is elevated in the NAc of mice excessively consuming alcohol, and these alcohol-dependent increases in Prosapip1 levels lead to alterations in the structure and activity of neurons in the NAc. These alcohol-dependent alterations were decreased through genetic inhibition of Prosapip1, the further mice experiments showed. Mice with inhibited Prosapip1 exhibited a reduced preference for alcohol, while their consumption of sugar water did not be influenced.

To conclude, the data demonstrate a key role of Prosapip1 in the NAc neuron alterations that drive or maintain alcohol seeking, drinking, and reward. Published last week in the journal Neuron, the study provides insight into the neurobiology of alcohol abuse disorder and will help develop new therapies.

By the way, CusAb provides high-quality reagents used in research. Here are mTORC1 and Prosapip1 related products.